|Donor Lymphocytes may Acquire Cytolytic Specificity to Donor′s Engrafted Hematopoietic Cells after a Hematopoietic Stem Cell Allograft Resulting in Marrow Failure|
|Xing, Haizhou; Ou, Yuan; Liu, Jing; Zhu, Ping|
|关键词||hematopoietic stem cell transplantation bone marrow failure immune reconstitution T-cell receptor|
|WOS标题词||Science & Technology|
|类目[WOS]||Medical Laboratory Technology|
|研究领域[WOS]||Medical Laboratory Technology|
|关键词[WOS]||GRAFT-VERSUS-HOST ; RECEPTOR REPERTOIRE ; CLONOTYPIC ANALYSIS ; TRANSPLANTATION ; LEUKEMIA ; RECONSTITUTION ; DISEASE ; BLOOD|
Background: Secondary rejection sometimes occurs after engraftment of allogeneic hematopoietic stem cell transplantation (allo-HSCT), which results in marrow failure. To clear possible reasons for BM failure, we observed a patient with acute myeloblastic leukemia who died of hematopoietic failure one year after apparently successful allo-HSCT.
Methods: The patient was a 44 year old male. Allo-HSCT was successful after 40 days, and 100% of marrow cells were of donor′s origin. Graft-versus-host disease (GVHD) began at the 60th day with involvement of multiple organs. He died of marrow failure on the 360th day after allo-HSCT.
Results: We identified the origin of the patient′s lymphocytes by a donor′s specific HLA locus, and a dominant T-cell clone by spectratyping of the TCRV beta subfamily on T-cells. The patient′s dominant CD8+ cells were separated by magnetic beads and incubated with donor′s cells or patient′s leukemic cells to evaluate their cytolytic specificity. TCR alpha and TCR beta cDNAs were cloned from the dominant CD8+ T-cells, transfected into Jurkat cells, and characterized the cytolytic specificity of the transfected Jurkat cells. In the period of 60 to 120th day after allo-HSCT, blood CD3+CD8+ cytotoxic T lymphocytes (CTLs) gradually increased and fluctuated in the range of 60 to 90%,CD3+CD4+ cells fluctuated in the range of 5 to 18%, and CD4+CD25+ cells accounted for between 3 to 13%. Spectratyping of the 24 TCRV beta subfamilies in blood lymphocytes demonstrated a dominant TCRV beta 13.1 clone with HLA-A*0201 of donor origin. The dominant CD8+ cells separated by magnetic beads showed cytolytic specificity to donor′s blood mononuclear cells (BMCs), but not to patient′s fibroblasts. Jurkat cells containing the cDNAs of TCR alpha and TCR beta chains cloned from the dominant CD8+ cell clone had cytolytic activity against donor′s BMCs, patient′s leukemic cells, and BMCs from an unrelated subject accounting for 43%, 15%, and 0.42%, respectively. The dominant lymphocyte clone of donor′s origin with CD3+CD8+ TCRV beta 13.1 markers in the patient may have been determinant in the hematopoiesis failure.
Conclusions: Donor′s lymphocytes changed in the recipient, acquiring the cytolytic specificity to donor′s hematopoietic cells and presumably leading to marrow failure.
|作者单位||Peking Univ, Hosp 1, Dept Hematol, Beijing 100034, Peoples R China|
|Xing, Haizhou,Ou, Yuan,Liu, Jing,et al. Donor Lymphocytes may Acquire Cytolytic Specificity to Donor′s Engrafted Hematopoietic Cells after a Hematopoietic Stem Cell Allograft Resulting in Marrow Failure[J]. CLINICAL LABORATORY,2014,60(3):455-462.|
|APA||Xing, Haizhou,Ou, Yuan,Liu, Jing,&Zhu, Ping.(2014).Donor Lymphocytes may Acquire Cytolytic Specificity to Donor′s Engrafted Hematopoietic Cells after a Hematopoietic Stem Cell Allograft Resulting in Marrow Failure.CLINICAL LABORATORY,60(3),455-462.|
|MLA||Xing, Haizhou,et al."Donor Lymphocytes may Acquire Cytolytic Specificity to Donor′s Engrafted Hematopoietic Cells after a Hematopoietic Stem Cell Allograft Resulting in Marrow Failure".CLINICAL LABORATORY 60.3(2014):455-462.|